In the coming year, the molecular basis of a genetically determined deficiency of the fourth component of complement in guinea pigs will be studied with a method for cell-free synthesis of C4 isolated polysomes. Attempts to isolate and translate normal C4 m-RNA will be undertaken in preparation for additional studies of the genetic lesion in C4 deficiency. The recently described precursor of guinea pig serum C4 (Pro-C4) will be isolated from normal liver and characterized. If this study is successful, the mechanism of conversion of Pro-C4 to C4 will be examined using the purified protein. Finally, these methods will be extended to study of other complement deficiency states and to the molecular basis of acquired changes in rates of complement biosynthesis. BIBLIOGRAPHIC REFERENCES: Strunk, R.S. and Colten, H.R.: Inhibition of the enzymatic activity of the first component of complement (C1) by heparin. J. Clin. Immun. and Immunopath. 6:248-255, 1976. Colten, H.R.: Biosynthesis of complement in Advances in Immunology. Eds. F.J. Dixon, and H. Kunkel, 1976, Vol. 22, pp. 67-119.